title: Preeclampsia is associated with the presence of transcriptionally active placental fragments in the maternal lung.
abstract: Preeclampsia is associated with increased levels of the circulating antiangiogenic factor sFlt-1 and with an excessive shedding of placenta-derived multinucleated syncytial aggregates into the maternal circulation. However, it remains unclear whether these aggregates are transcriptionally active in the maternal organs and can, therefore, contribute to the systemic manifestations of preeclampsia. In this study, we measured placental soluble fms-like tyrosine kinase-1 (sFlt-1) mRNA levels in preeclamptic- and control placentas and performed RNA in situ hybridization to localize the main placental expression site of sFlt-1 mRNA. Because the maternal lung is the first capillary bed that circulating syncytial aggregates traverse, we studied the presence and persistence of placental material in lungs of preeclamptic and control subjects. To confirm the placental origin of these aggregates in maternal lungs, immunohistochemistry for the placenta-specific marker hCG (human chorionic ghonadotropin) and Y chromosome in situ hybridization were performed. Using human placental tissue, we found that syncytial knots are the principal site of expression of the antiangiogenic factor sFlt-1. In addition, autopsy material obtained from women with preeclampsia (n=9) showed significantly more placenta-derived syncytial aggregates in the lungs than in control subjects (n=26). Importantly, these aggregates still contained the antiangiogenic factor sFlt-1 after their entrapment in the maternal lungs. The current study confirms the important role of syncytial knots in placental sFlt-1 mRNA production. In addition, it shows a significant association between preeclampsia and larger quantities of sFlt-1 containing syncytial aggregates in maternal lungs, suggesting that the transfer of syncytial aggregates to the maternal compartment may contribute to the systemic endothelial dysfunction that characterizes preeclampsia.
authors.affiliation: Leiden University Medical Center, Department of Pathology, L1 Q, PO Box 9600, P0-107, 2300 RC Leiden, The Netherlands.
authors.forename: Aletta J
authors.initials: AJ
authors.lastname: Buurma
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Penning
authors.forename: Frans
authors.initials: F
authors.lastname: Prins
authors.forename: Joke M
authors.initials: JM
authors.lastname: Schutte
authors.forename: Jan Anthonie
authors.initials: JA
authors.lastname: Bruijn
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wilhelmus
authors.forename: Augustine
authors.initials: A
authors.lastname: Rajakumar
authors.forename: Kitty W M
authors.initials: KW
authors.lastname: Bloemenkamp
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Baelde
mesh_terms: D000328:Adult; D006063:Chorionic Gonadotropin / Q000378:metabolism; D041322:Chromosomes, Human, Y / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000378:metabolism; D014599:Uterus / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: endothelial cells; hypertension, pregnancy-induced; placental circulation; preeclampsia; sFlt-1 protein, human